Can Kisqali® (Ribociclib) effectively target triple-negative breast cancer? A computational insight on potential mechanisms and therapeutic strategies

Triple-negative breast cancer (TNBC), which represents 15–20% of all breast cancers, is a highly aggressive subtype distinct by the absence of estrogen, progesterone, and HER2 receptors, with few targeted therapies available. Present study explores Kisqali® (Ribociclib)'s therapeutic potential against TNBC using a computational approach to identify key molecular targets and binding interactions. Ribociclib binds strongly to proteins associated with TNBC progression, such as RelA (− 8 kcal/mol), HER2 (− 8.1 kcal/mol), GSK3β (− 7.8 kcal/mol), and Hsp90α (− 7.1 kcal/mol). Ribociclib superior to native ligands for RelA, HER2, and GSK3β in terms of binding stability, with strong hydrogen and hydrophobic interactions. Ribociclib inhibits key pathways such as NF-κB, Wnt signaling, and tumor cell metabolism, demonstrating its multifaceted mechanism of action. Molecular dynamic (MD) simulations indicated minimal fluctuations, suggesting the formation of stable complexes between ribociclib and HER2 (7PCD). HER2 was utilized for simulations because of its favorable binding interactions, docking scores, binding affinity, and structural stability. Computational results suggest Ribociclib's potential for TNBC treatment, but further preclinical and clinical studies are needed to confirm its efficacy. This research lays foundations for future Ribociclib-based approaches to improving TNBC patient care.